Molecular Diagnosis of Malaria Infection: A Survey in a Hospital in Central Italy

Malaria is a dramatic disease caused by the protozoan parasites Plasmodium. The diagnosis is mainly based on microscopy and rapid diagnostic tests (RDT). Molecular approaches based on PCR techniques may be an alternative tool particularly favourable in regions with declining prevalence. This work aimed to assess pros and cons of molecular diagnosis of malaria in a district of Central Italy were several tens of imported malaria cases are diagnosed every year. Thirty-three blood samples were analysed by microscopy, RDT and molecular techniques to monitor the relative efficiency in malaria diagnosis. Molecular analysis and microscopy diagnosed 32 out of 33 samples as positive for malaria, while RDT only 29. More differences concerned the diagnosis of mixed infections. Our findings remark the importance of the molecular approach in supporting and improving malaria diagnosis. In the cases here presented, the molecular analysis was particularly useful to unveil parasites presence in infections not detectable by blood smear analysis and to additionally solve real and/or presumed mixed infections

Temporal dynamics of the ABC transporter response to insecticide treatment: insights from the malaria vector Anopheles stephensi

In insects, ABC transporters have been shown to contribute to defence/resistance to insecticides by reducing toxic concentrations in cells/tissues. Despite the extensive studies about this detoxifying mechanism, the temporal patterns of ABC transporter activation have been poorly investigated. Using the malaria vector Anopheles stephensi as a study system, we investigated the expression profile of ABC genes belonging to different subfamilies in permethrin-treated larvae at different time points (30 min to 48 h). Our results showed that the expression of ABCB and ABCG subfamily genes was upregulated at 1 h after treatment, with the highest expression observed at 6 h. Therefore, future investigations on the temporal dynamics of ABCgene expression will allow a better implementation of insecticide treatment regimens, including the use of specific inhibitors of ABC efflux pumps

Facing Malaria Parasite with Mosquito Symbionts

Optical physic

Chapter Facing Malaria Parasite with Mosquito Symbionts

Optical physic

Staging of osteonecrosis of the jaw requires computed tomography for accurate definition of the extent of bony disease

Management of osteonecrosis of the jaw associated with antiresorptive agents is challenging, and outcomes are unpredictable. The severity of disease is the main guide to management, and can help to predict prognosis. Most available staging systems for osteonecrosis, including the widely-used American Association of Oral and Maxillofacial Surgeons (AAOMS) system, classify severity on the basis of clinical and radiographic findings. However, clinical inspection and radiography are limited in their ability to identify the extent of necrotic bone disease compared with computed tomography (CT). We have organised a large multicentre retrospective study (known as MISSION) to investigate the agreement between the AAOMS staging system and the extent of osteonecrosis of the jaw (focal compared with diffuse involvement of bone) as detected on CT. We studied 799 patients with detailed clinical phenotyping who had CT images taken. Features of diffuse bone disease were identified on CT within all AAOMS stages (20%, 8%, 48%, and 24% of patients in stages 0, 1, 2, and 3, respectively). Of the patients classified as stage 0, 110/192 (57%) had diffuse disease on CT, and about 1 in 3 with CT evidence of diffuse bone disease was misclassified by the AAOMS system as having stages 0 and 1 osteonecrosis. In addition, more than a third of patients with AAOMS stage 2 (142/405, 35%) had focal bone disease on CT. We conclude that the AAOMS staging system does not correctly identify the extent of bony disease in patients with osteonecrosis of the jaw

Drug Design for CNS Diseases: Polypharmacological Profiling of Compounds Using Cheminformatic, 3D-QSAR and Virtual Screening Methodologies.

HIGHLIGHTS Many CNS targets are being explored for multi-target drug designNew databases and cheminformatic methods enable prediction of primary pharmaceutical target and off-targets of compoundsQSAR, virtual screening and docking methods increase the potential of rational drug design The diverse cerebral mechanisms implicated in Central Nervous System (CNS) diseases together with the heterogeneous and overlapping nature of phenotypes indicated that multitarget strategies may be appropriate for the improved treatment of complex brain diseases. Understanding how the neurotransmitter systems interact is also important in optimizing therapeutic strategies. Pharmacological intervention on one target will often influence another one, such as the well-established serotonin-dopamine interaction or the dopamine-glutamate interaction. It is now accepted that drug action can involve plural targets and that polypharmacological interaction with multiple targets, to address disease in more subtle and effective ways, is a key concept for development of novel drug candidates against complex CNS diseases. A multi-target therapeutic strategy for Alzheimer's disease resulted in the development of very effective Multi-Target Designed Ligands (MTDL) that act on both the cholinergic and monoaminergic systems, and also retard the progression of neurodegeneration by inhibiting amyloid aggregation. Many compounds already in databases have been investigated as ligands for multiple targets in drug-discovery programs. A probabilistic method, the Parzen-Rosenblatt Window approach, was used to build a "predictor" model using data collected from the ChEMBL database. The model can be used to predict both the primary pharmaceutical target and off-targets of a compound based on its structure. Several multi-target ligands were selected for further study, as compounds with possible additional beneficial pharmacological activities. Based on all these findings, it is concluded that multipotent ligands targeting AChE/MAO-A/MAO-B and also D1-R/D2-R/5-HT2A -R/H3-R are promising novel drug candidates with improved efficacy and beneficial neuroleptic and procognitive activities in treatment of Alzheimer's and related neurodegenerative diseases. Structural information for drug targets permits docking and virtual screening and exploration of the molecular determinants of binding, hence facilitating the design of multi-targeted drugs. The crystal structures and models of enzymes of the monoaminergic and cholinergic systems have been used to investigate the structural origins of target selectivity and to identify molecular determinants, in order to design MTDLs

PHACES syndrome: Diode laser photocoagulation of intraoral hemangiomas in six young patients

AbstractIntroductionThe acronym PHACES describes the association of posterior fossa malformations, facial hemangiomas, arterial anomalies (cardiovascular or cerebrovascular), coarctation of the aorta and cardiac defects, eye abnormalities, and sternal or ventral defects. In this study we report on 6 patients affected by the PHACES syndrome and showing 34 intraoral hemangiomas (IH), treated by diode laser photocoagulation (DLP).Case presentationIH appeared as red-bluish soft masses, smooth or lobulated, from a few millimetre to several centimetres in size, covered by intact mucosa and blanching on pressure. IHs were treated by DLP with 320μm fibres at a wavelength of 800±10nm. The diode laser techniques applied were: Transmucosal DLP (DLTP), a no-contact technique in which laser energy is delivered by a flexible optic quartz fiber, which is kept 2–3mm apart from the lesion, and Intralesional DLP (DLIP), in which the fibre is introduced into the lesion through a transmucosal access. DLTP was used for 20 flat, superficial IHs and, after a variable number of laser sessions (average=3) depending on the size of the lesion, 65% completely regressed, while in the remaining 35% shrinkage of the lesion was achieved with minor and few complications.The remaining 14 deep/multi-lobulated IHs were treated by DLIP, resulting in complete regression of 79% of them.ConclusionsDLP techniques are an effective and minimally invasive procedure for IH in patients with PHACES, in consideration of the multiple lesions to treat, of the necessity of multiple interventions and the higher compliance of the patients

TRADITIONAL AND CLSM EXAMINATIONS IN A CASE OF ELECTROCUTION: NEW HISTOPATHOLOGICAL SIGNS

We described for the first time the morphological alterations of epicardic cardiac nerve trunks due to electricity. All these alterations can seriously interfere with transmission mechanism of nerve impulses. Central endoneural clefts of the nerve fibers with perineurium detachment could be used in future as specific signs of the passage of the electrical current through the heart. We recommend heart specimens at the level of common trunk of the left coronary artery in all the cases of suspected electrocution, to better evaluate cardiac nerve trunks damages and alterations

Symbiotic Control of mosquito borne disease

It is well accepted that the symbiotic relationships insects have established with several microorganisms have had a key role in their evolutionary success. Bacterial symbiosis is also prevalent in insects that are efficient disease vectors, and numerous studies have sought to decrypt the basic mechanisms of the host-symbiont relationships and develop ways to control vector borne diseases. "Symbiotic control", a new multi-faceted approach that uses symbiotic microorganisms to control insect pests or reduce vector competence, seems particularly promising. Three such approaches currently at the cutting edge are: i) the disruption of microbial symbionts required by insect pests; ii) the manipulation of symbionts that can express anti-pathogen molecules within the host; and iii) the introduction of endogenous microbes that affect life-span and vector capacity of the new hosts in insect populations. This work reviews current knowledge on microbial symbiosis in mosquitoes that holds promise for development of symbiotic control for mosquito borne diseases